Cholinergic Circuitry in Auditory Brainstem

听觉脑干中的胆碱能回路

• 批准号: 7276263
• 负责人: Susan Diane Motts
• 金额: $ 2.5万
• 依托单位: NORTHEAST OHIO MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7276263
• 关键词: Acetylcholine; Acoustics; Address; Age; Aging; Area; Arousal; Auditory; Auditory system; Axon; Brain; Brain Stem; Cell Nucleus; Cells; Cholinergic Agents; Cholinergic Agonists; Cholinergic Receptors; Complex; Data; Disease; Dorsal; Electron Microscopy; Frequencies; Functional disorder; Immunohistochemistry; Individual; Inferior Colliculus; Knowledge; Lateral; Localized; Medial; Neuromodulator; Pathway interactions; Pedunculopontine Tegmental Nucleus; Physiological; Play; Presbycusis; Process; Property; Public Health; Range; Reporting; Role; Sensory; Sleep Wake Cycle; Source; Stimulus; Structure; Suggestion; Synapses; System; Tegmentum Mesencephali; Testing; Thalamic structure; Visual system structure; Work; auditory nuclei; auditory pathway; cholinergic; design; gamma-Aminobutyric Acid; insight; research study; response; sensory system

DESCRIPTION (provided by applicant): The inferior colliculus (1C) is a central structure in the brainstem auditory pathways and processes almost all ascending auditory sensory information. Acetylcholine is a well-studied neuromodulator and is reported to modulate the responses of cells in the 1C to acoustic stimuli. The vast majority of 1C cells respond to cholinergic agonists, and cholinergic receptors have been localized throughout the 1C. Cholinergic effects contribute to a variety of response properties, including setting a general level of sensitivity as well as altering the selectivity of a cell for properties such as stimulus frequency. There are also suggestions that cholinergic inputs can activate inhibitory circuits in the 1C, but the targets of the cholinergic axons are unknown. Overall, interpreting the results of physiological studies has been hindered by a lack of data on the cholinergic circuitry. Even the source of cholinergic input to the 1C is unknown. Characterizing this circuitry will be an important step in understanding the roles of acetylcholine in auditory function. Multilabel retrograde tracing, immunohistochemistry, and electron microscopy will be used to identify the source(s) of cholinergic input to the 1C and to characterize their collateral projections and synaptic targets Relevance to Public Health: The proposed experiments will fill a large gap in our understanding of cholinergic circuits as they relate to the 1C. A greater understanding of this circuitry will provide a framework for interpreting experiments relating to many aspects of 1C function, as well as experiments related to arousal, sleep/wake cycles, and age- related hearing loss. A better understanding of the circuitry will provide an opportunity to expand our knowledge of the function and dysfunction of the auditory system and will provide insights into the design of new experiments relating to auditory system disorders.

描述（由申请人提供）：下丘（1C）是脑干听觉通路的中心结构，处理几乎所有上行听觉感觉信息。乙酰胆碱是一种经过充分研究的神经调节剂，据报道可以调节 1C 细胞对声刺激的反应。绝大多数 1C 细胞对胆碱能激动剂有反应，并且胆碱能受体分布在整个 1C 区域。胆碱能效应有助于多种反应特性，包括设置一般的敏感性水平以及改变细胞对刺激频率等特性的选择性。也有人认为胆碱能输入可以激活 1C 中的抑制回路，但胆碱能轴突的目标尚不清楚。总体而言，由于缺乏胆碱能回路数据，对生理研究结果的解释受到了阻碍。甚至 1C 的胆碱能输入来源也是未知的。表征该电路将是理解乙酰胆碱在听觉功能中的作用的重要一步。多标记逆行示踪、免疫组织化学和电子显微镜将用于识别 1C 胆碱能输入的来源，并表征其侧枝投射和突触目标 与公共健康的相关性：拟议的实验将填补我们理解中的巨大空白与 1C 相关的胆碱能回路。对该电路的更深入了解将为解释与 1C 功能的许多方面相关的实验以及与觉醒、睡眠/觉醒周期和年龄相关的听力损失相关的实验提供一个框架。对电路的更好理解将为我们扩展对听觉系统功能和功能障碍的了解提供机会，并将为与听觉系统疾病相关的新实验的设计提供见解。